Abstract

Background Major depression in childhood or adolescence increases
the riskof affective disorder in adulthood. The precise nature and course of
the subsequent disorder remain unclear.

Aims To investigate long-term psychiatric outcome of school-age
depression in community and clinic samples.

Method A group of 113 young adults were followed up after a mean of
7.8 years (s.e.=15).

Results Groups with persistent and recurrent depression were
identified. Recurrence of affective disorder was similar in clinic and
community groups. The clinic group had significantly longer index episodes;
these were predicted by an early psychiatric history, longer episode duration
before treatment and greater impairment. Being female, having higher
self-report depression scores and comorbidity at index episode predicted
earlier recurrence. Males were more likely to have persistentdepression.

Conclusions Prognosis is similar in young people with depression
from community and clinical samples. Boys from a clinical sample are at higher
risk than girls of becoming persistently and severely mentally ill.

For many young people with depression their subsequent adult life is
punctuated by recurrent episodes of depression and poor psychosocial
functioning (Harrington & Dubicka,
2001). Recurrence rates are estimated to be 60–70%
(Birmaher et al,
1996). It is unclear which factors exert the most potent influence
on the course of the illness. Methodological differences may partly explain
this: some studies have not conducted diagnostic interviews in person at
baseline and follow-up, most did not collect data continuously throughout the
follow-up period, and impairment criteria may or may not have been
implemented. To our knowledge, the longitudinal, catch-up study reported here
is the first in the UK to carry out full diagnostic interviews, face-to-face,
at baseline and follow-up, to apply strict criteria for impairment at both
time points and record follow-up data continuously from baseline. Outcome is
examined in terms of recovery from the index episode of depression and first
recurrence in clinically referred and community populations.

METHOD

Sample

A sample of 193 young people aged 8–17 years was available for
follow-up: 120 clinically referred, 35 from the community and 38 controls. All
had participated in previous studies by our group in the 1990s. The control
group was retained in this study to examine whether risk for recurrence might
be influenced by periodicity effects (i.e. that there are unique features
associated with adolescents ascertained in the 1990s).

Clinic and control groups

The clinic group comprised patients aged 8–16 years attending two
child and adolescent mental health clinics in the Cambridge area: 92 were
recruited in 1991–2 and 28 in 1995–6. The 38 well controls (no
psychiatric disorder), from the same geographical area, were recruited through
general practitioners in 1991–2 and were matched for age and gender to
every third patient with depression. Participants were interviewed at study
entry and 36 weeks later. For this study, information from these assessments,
together with details from clinical notes, was pooled to designate the ‘
index’ episode.

Community group

The 35 community participants, aged 12–17 years, were recruited from
Cambridge-shire schools to participate in a large community depression study
in 1994–5. All were illness-free at entry. After 1 year a proportion of
these young people were either depressed or had been depressed in the interim:
these provided the sample for follow-up.

Follow-up assessment. Current and lifetime diagnoses were
generated using the Structured Clinical Interview for DSM–IV Axis I
Disorders (SCID–I; American
Psychiatric Association, 1994), Patient Edition
(First et al, 1997).
We screened for antisocial and borderline personality disorders using an
adapted screen from the Structured Clinical Interview for DSM–IV Axis II
Disorders (SCID–II; Spitzer et
al, 1990). Positive responses were followed up using the
relevant section of the SCID–II interview.

Note ondiagnosis. At baseline, a proportion of people in the
clinic group had experienced an episode of major depressive disorder within an
episode of dysthymia (double depression). It was impossible to distinguish
accurately the onset and offset of major depression within the dysthymic
episode. Therefore, index episodes of depression are rated from onset to
offset of significant depressive symptoms, with no attempt to delineate full
major depressive disorder from dysthymia.

Puberty

Baseline assessment. Participants in the clinic group were shown
gender-appropriate sketches relating to the five standard Tanner stages of
pubertal development (Tanner,
1962) and asked to select which looked ‘most like
them’. Participants were grouped as pre-/early puberty (Tanner stages I
and II) or mid/late puberty (Tanner stages III–V). The stage of puberty
was not assessed in the community group.

Timeline

Follow-up assessment. The use of a timeline proved invaluable in
orienting participants to the lengthy follow-up period. A timeline was drawn
from the date of the last interview to the current interview. Interviewee and
interviewer chronologically mapped significant life events on the timeline,
for example school leaving, examinations, relationships, losses, followed by
episodes of illness, good health, treatment and medication.

Data collection

Tracing procedure

Recorded deaths since baseline were checked using the ‘
list-cleaning’ service provided by the Office for National
Statistics. Participants were contacted by letter through their family of
origin or through their general practitioner by way of their strategic health
authority.

Follow-up interview

Participants were interviewed as soon after their 22nd birthday as
possible. The eldest were approached first, from July 2000. Follow-up
interviewing lasted for 31 months. Follow-up time was calculated from the date
of each participant’s last baseline interview (in adolescence) to the
date of their follow-up interview (as young adults). Interviews were conducted
by four trained research staff, masked to baseline diagnoses and ascertainment
group. Diagnoses were reached by consensus with a clinician (I.G.).
Reliability was acceptable (κ > 0.8). Participants gave written
consent to both the interview and access to clinical notes. Participants were
seen either at home or at the Developmental Psychiatry Section in Cambridge. A
small remuneration was offered. The study received the full approval of the
local and regional ethics committees.

Statistical procedures

Analysis was carried out using the Statistical Package for the Social
Sciences, version 10.0 for Windows. Mann–Whitney U-tests were
used on non-parametric data and t-tests on parametric data. Time to
full remission (defined as a minimum of 2 months free of depressive symptoms
and functional impairment) of the index episode of depression and time from
full remission to first depressive recurrence (defined as a new depressive
episode following a period of full remission) were examined using
Kaplan–Meier survival analysis. (This method takes into account the
assessment periods of people for whom the event of interest has not occurred
by the end-point of the study, defining them as ‘censored’. Here,
these are participants whose index episode of depression had not fully
remitted and those who had not experienced a depressive recurrence by the time
of their follow-up interview.) As those interviewed were unable to reliably
pinpoint onsets and offsets accurately, times were recorded and entered to the
nearest 0.25 of a year. Survival curves were compared using the log-rank test.
In the clinic group, Cox regression was used to examine baseline factors
thought to influence time to full remission and time to first depressive
recurrence.

RESULTS

Non-participants

Clinic patients proved significantly more difficult to follow up than young
people from the community or controls (55% v. 71% and 79%
respectively: χ2=8.47, d.f.=2, P=0.014). Participants
and nonparticipants were compared on a number of baseline variables.
Significant differences were found only within the clinic group:
non-participants were significantly younger at the onset of their index
episode of depression (mean 12.1 years v. 13.5 years,
z=72.72, P=0.006), more likely to have been pre-pubertal or
in the early stages of puberty (v. mid to late puberty) (28 (61%)
v. 26 (35%), χ2=7.59, d.f.=1, P=0.006), have
less psychiatric illness among first-degree relatives (27 (56%) v. 23
(36%), χ2=4.58, d.f.=1, P=0.032) and have parents who
had completed their education by age 16 years: mothers 37 (64%) v. 15
(27%), χ2=15.16, d.f.=1, P<0.001; fathers 29 (63%)
v. 22 (36%), χ2=7.65, d.f.=1, P=0.006.

Success of tracing, sample response and exclusions

Table 1 compares
participation according to ascertainment group. Of the original 193
participants, 191 were traced (99%). Of these, 121 (63%) were interviewed, 29
(15%) refused, 38 (20%) did not respond and 3 (2%) were out of the UK. Of the
121 interviewed, 8 were subsequently excluded: 1 for medical reasons and 7
because their index episodes were nonaffective.

Final sample

Data reported here are based on 113 participants: 58 clinic and 25
community participants all with depression (major depression, minor depression
or dysthymia) in childhood or adolescence, and 30 depression-free controls.
Mean follow-up times differed significantly between groups: 8.1 years
(s.d.=1.3), 5.8 years (s.d.=0.6) and 9.2 years (s.d.=0.81) for clinic,
community and control groups respectively (Kruskal–Wallis χ
2=59.86, d.f.=2, P<0.001). Univariate comparisons
(Mann–Whitney) showed differences were significant between all three
groups (clinic v. controls z=3.78, P<0.001;
clinic v. community z=6.43, P<0.001; community
v. controls z=76.34, P<0.001).

Mean age at follow-up interview was 23 years (s.d.=1.66), 22 years
(s.d.=0.79) and 23.5 years (s.d.=1.6) for the clinic, community and control
groups respectively (clinic v. community t=2.88,
P=0.005; community v. controls t=4.07,
P<0.001).

Baseline characteristics

Table 2 gives the
characteristics of the sample at baseline. Compared with the community group,
participants in the clinic group were more severely impaired, had higher rates
of attempted suicide and self-harm, more psychotic symptoms, were
significantly younger at onset of depression, received more treatment and
medication and had significantly more psychiatric illness among first-degree
relatives. Self-report depression scores were no different between the clinic
and the community groups; both were significantly higher than controls.

Subsequent disorder

Figure 1 compares subsequent
psychiatric illness in the ascertainment groups. By the time of their
follow-up interview 24 of 30 controls (80%) had remained illness-free compared
with 16 of 58 clinic patients (28%) (Fisher’s exact test
P=0.001) and 10 of 25 young people from the community (40%)
(Fisher’s exact test P=0.005). As the focus of this report is
depression we do not report on those who had exclusively non-affective
illness.

Recurrent episodes of depression (one to three further episodes) were
experienced by 20 people in the clinic group (35%) and 12 in the community
group (48%), whereas 13 (22%) and 2 (8%) respectively had persistent
depression since the index episode. Four people in the control group (14%)
experienced first depressive episodes.

In the clinic group with subsequent affective disorder (33, consisting of
10 men and 23 women), men were more likely than women to be persistently
depressed: 7 (70%) v. 6 (26%); whereas women were more likely to have
recurrent episodes, 17 (74%) v. 3 (30%): (Fisher’s exact test
P=0.026).

No completed suicide was recorded during the follow-up period. There was a
trend for more suicidal ideation and attempts in the intervening years among
the clinic group (19 of 58; 33%) compared with the community group (3 of 25;
12%); Fisher’s exact test P=0.06. In the control group, one
person experienced suicidal ideation but there was no suicide attempt.

Index depression

The index episode of depression fully remitted in 45 clinic patients (78%)
and 23 from the community (92%). Kaplan–Meier survival analysis was
carried out to examine predictors of time to full remission. The 13 clinic
patients (22%) and the 2 from the community (8%) in whom the index episode did
not remit are censored in the analysis. (‘Full remission’ refers
to depression; comorbid symptoms might have persisted.)

Figure 2 compares the
cumulative survival times to full remission. The median time to full remission
in clinic patients was 2 years (95% CI 0.83–3.17) v. 3 months
in the community. By 3 months after onset, remission had occurred in 3 clinic
patients (5%) compared with 17 (68%) in the community. By the end of the first
year numbers in remission were 16 (28%) and 22 (88%) and by 2 years 29 (50%)
and 23 (92%) for clinic and community groups respectively. Remission rates
were clearly different (log-rank test χ2=25.1, d.f.=1,
P<0.001) and so further analysis was made of the two groups
separately.

Time to full remission of index depression: comparison of clinic group
(, n=58, 45
remitted (78%), 13 (22%) censored/unremitted at 7–13.7 years) and the
community group (-------, n=25, 23 remitted (92%), 2 (8%)
censored/unremitted, both at 6 years).

Cox regression (clinic patients only)

Eight baseline variables were entered into a Cox regression (backwards
linear regression): gender, pubertal stage at onset, MFQ score, age at onset
of index episode of depression, age at first psychiatric episode, comorbidity
at index episode, severity of impairment at index episode and number of months
with depression before starting treatment. The best-fit model incorporated
three variables. The longest times to remission were found in those most
severely impaired at index (hazard ratio (HR)= 3.27, 95% CI 1.6–6.65,
Wald=10.62, d.f.=1, P=0.001), those who were depressed for longer
(months) before starting treatment (HR=0.95, 95% CI 0.92–0.99,
Wald=5.51, d.f.=1, P=0.019) and those with early psychiatric episodes
(HR=1.12, 95% CI 1–1.24, Wald=4, d.f.=1, P=0.046).

Owing to small numbers, missing data and skewed distribution, Cox
regression analysis of the community sample was not possible.

First recurrence of depression

Clinic group

Survival analysis explored time from full remission to first recurrence of
depression, necessarily including only those whose index episode of depression
had remitted (n=45). Of these, 20 (44%) experienced at least one
recurrence of depression. The 25 (56%) whose depression did not recur are
censored in the analysis. Figure
3 shows the cumulative recurrence rate. The median time to first
recurrence was 9.25 years (95% CI 8.64–9.86). By 1 year after remission
only 1 (2%) had experienced recurrence, after 2 years 5 (11%), after 3 years 8
(18%), 4 years 9 (20%), 5 years 13 (29%) and 6 years 15 (34%). In 3 instances
the person was well for 9 years before the depression recurred. Recurrence
peaked at 9% in years 1–2 and 4–5.

Clinic group: time to first recurrence of depression from onset of full
remission (n=45: 20 recurrences (44%), 25 (56%) censored (no
recurrence); first censored observation (+)3.75 years, last 9 years).

The following baseline predictors of time to recurrence were entered in a
Cox regression (backwards linear regression): gender, MFQ score, comorbidity,
severity of impairment, pubertal stage and age at onset. The best-fit model
was obtained with three variables: earlier recurrence was associated with
being female (HR=5.4, 95% CI 1.12–25.73, Wald=4.42, d.f.=1,
P=0.036), higher self-report depression scores (MFQ) at index episode
(HR=1.04, 95% CI 0.999–1.1, Wald=3.73, d.f.=1, P=0.053) and
comorbid symptoms at index episode (HR=3.3, 95% CI 0.952–11.3,
Wald=3.54, 3.54, d.f.=1, P=0.06). There was no interaction. Mean
duration of first recurrence was 45 weeks (s.d.=36.5) with a mean age at onset
of 20 years (s.d.=1.8).

Community group

Small numbers made survival analysis impossible. Calculated in the standard
way, mean time to first recurrence (n=12) was 3.4 years (s.d.=1.5).
The mean duration of first recurrence was 44 weeks (s.d.=53.3) with a mean age
at onset of 19.5 years (s.d.=2).

Controls

The mean age at onset of new episodes was 19 years, and the mean duration
was 41 weeks (s.d.=42.2).

Group with persistent depression

The mean duration of depression, from onset in adolescence through to
follow-up in young adult life, was 9.6 years (s.d.=2, range 7–13.8). The
original diagnoses of the 15 people with non-remitted depression were 3 (20%)
pure depression, 7 (47%) depression/anxiety, 5 (33%) multiple comorbidity.
Most had complex diagnostic profiles with persistent depression remaining a
core feature. One individual was subsequently diagnosed as having
schizophrenia; one had bipolar affective disorder (also substance dependency);
three people experienced other psychotic episodes (two also
substance-dependent); three became dysthymic (one also substance-dependent);
three had persistent anxiety symptoms (one also substance-dependent); and four
had ‘pure’ persistent depression. Five participants (33%) had
repeated in-patient stays during the follow-up period. Non-adherence to
treatment (defined as a pattern of missed appointments, withdrawal from
treatment, discharging self from hospital and refusing prescribed medication)
was significantly higher in this group than among those with recurrent
depression: 8 of 15 (53%) compared with 6 of 31 (19%; Fisher’s exact
test P=0.04).

There were significantly more suicide attempts and suicidal ideation among
the group with persistent depression than among the recurrent depression
group: 13 of 15 (87%) v. 6 of 32 (19%; Fisher’s exact test
P=0.001).

Substance and alcohol use

During follow-up

Recreational use or no use of substances and alcohol was reported by 36
(63%), 19 (76%) and 23 (77%) of the clinic, community and control groups
respectively. However, many of these reported regular, high levels of
recreational use. Commonly, cannabis, amphetamines and/or alcohol were used
2–3 times per week, with use increasing over time. However, little or no
functional impairment was reported. Dependence was coded according to
DSM–IV criteria. At least one episode of prolonged, daily (or near-daily
for more than 6 months) substance or alcohol misuse was reported by 15 people
in the clinic group (26%), 4 in the community group (16%) and 7 in the control
group (23%) (NS). Prolonged polysubstance/alcohol misuse or dependence was
absent in the control group but was reported by 6 (11%) of the clinic sample
and 2 (8%) of the community sample (missing data on 1 clinic patient;
n=57).

Current use

At follow-up, dependency rates in the clinic and community groups were 5
(9%) and 1 (4%) respectively: in the clinic group 2 persons were dependent on
heroin, 2 on prescribed medication (with substantial overuse) and 1 on
alcohol; the person from the community group was alcohol-dependent. All were
depressed. There was no dependence among the controls. A further 3 clinic
(5%), 1 community (4%) and 2 control (7%) participants reported current, daily
cannabis use or alcohol use for at least 6 months, but only one of the clinic
group met impairment criteria.

Community group

Eight participants (32%) had a current diagnosis at follow-up interview: 6
affective disorder (4 major depressive disorder, 1 dysthymia, 1 bipolar
disorder) and 2 anxiety disorder. In 3 instances (12%) the participant was
currently receiving treatment (1 out-patient care, 2 general practitioner
care) and were taking psychotropic medication. The mean BDI score was 8
(s.d.=5.6, range 0–19). Community participants were as likely as clinic
patients to have a current diagnosis.

Controls

Three people in the control group (10%) were diagnosed with an affective
disorder at follow-up interview: 1 bipolar disorder, 1 depression and 1 minor
depression with comorbid eating disorder symptoms (eating disorder not
otherwise specified). Both those with bipolar and major depression were
receiving psychiatric treatment and psychotropic medication. The mean BDI
score was 5 (s.d.=5.1, range 0–25).

DISCUSSION

Continued affective disorder was present in over half those with
childhood/adolescent depression from both clinic and community groups. For a
substantial proportion (40%) depression was recurrent with significant periods
of remission. A small but significant subgroup (18%) of individuals remained
persistently unwell into adulthood. In the clinic group, those whose index
episode remitted took significantly longer to recover than those from the
community. Females were more liable to recurrence, males to persistence.

Persistent depression

To our knowledge, previous studies have not identified a group whose
adolescent depression continued, unabated, into young adulthood. This may be
for methodological reasons. For example, Weissman et al
(1999a,
b) left an arbitrary
gap of 12 months between baseline and follow-up in an attempt not to confuse
index and subsequent episodes. Similarly, others, whose primary focus was
adult recurrence, recorded baseline data at around 13 years and follow-up data
from 17 years (Harrington et al,
1990; Fombonne et al,
2001). This strategy runs the risk of misclassification, with
persistent depression being incorrectly classified as recurrent. Our study
overcame this by collecting data continuously from baseline throughout the
follow-up period. The result is the identification of a small group (more
males than females) with unremitting mental illness. These patients are
characterised by more severe impairment than those described in previous
studies, in which partial remissions occurred with ongoing residual symptoms
(reviewed by Birmaher et al,
2002).

For most of those with persistent depression (80%), the index episode of
depression was accompanied by at least one comorbid disorder. Complex
diagnostic profiles evolved, including high rates of psychotic illness (30%),
dependence (30%) and suicidal thoughts or attempts (87%). In over half (53%),
the patient regularly did not adhere to treatment. The Cox regression
suggested that, as adolescents, these individuals had been depressed for long
periods before starting treatment and had been severely impaired. Within the
clinic group, first-onset depression may exert a more deleterious effect on
males compared with females, but neither age nor pubertal status at first
episode contributed to the outcome. These patients might benefit from early,
long-term and more intensive clinical intervention than is currently
given.

Remission and recurrence in the community group

The adolescents ascertained from the community on the whole achieved
remission from their first depressive episode: 68% by 3 months and 92% by 3
years. This may be explained by less severe index episodes characterised by
the absence of suicide attempts and psychotic features, a near-absence of
self-harm and only moderate impairment. Despite this, almost half (48%)
experienced recurrence of their depression, which is consistent with the 45%
recurrence rate reported by Lewinsohn et al
(1999). First recurrences were
similar in length to those experienced in the clinic group. The small size of
this community group means that the results should be treated with caution.
They suggest that the probability of recurrence is high despite the moderate
nature of the original depressive episode. A small proportion of individuals
from the community may suffer persistent depression, with no remission, into
young adulthood. Young people in the community with depression, therefore,
might benefit from early detection and robust intervention.

Remission and recurrence in the clinic group

Remission of the index episode of depression was slower among clinic
patients: only 5% had achieved remission by 3 months, less than a third by 12
months and only half by 3 years. Median time to full remission was 2 years,
with 13 (22%) having no remission by follow-up. This contrasts with previous
studies which have reported rates of 92% remission by 18 months
(Kovacs et al,
1984)–our 18-month figure was 38% – and 80% after 12
months (McCauley et al,
1993). This may be a result, in part, of our not differentiating
between dysthymia and major depressive disorder at the index assessment.
Kovacs et al (1984)
reported a pattern in dysthymia that more closely resembles that reported
here: a median duration of around 3 years, low annual remission rates and a
maximal remission of 89% after 6 years.

Longer index episodes were associated with more severe impairment, being
depressed for longer before starting treatment and having an early psychiatric
episode. In those with higher self-report depression (MFQ) scores and
comorbidity at index assessment the depression tended to recur sooner, and
recurrence was earlier in females than in males. There was no effect of
puberty or age. Confidence intervals were wide in our Cox regression,
indicating a less-than-perfect fit which could be a result of the wide
distribution of times to first recurrence (6 months to 9.75 years) and the
small number of males (n=3) who experienced recurrence compared with
females (n=17).

Females with depression were more likely to have a recurrent pattern of
depressive disorder, whereas more males developed persistent mental illness.
The non-participants in the follow-up constituted 45% of the original clinic
group, were younger and had less psychiatric illness among first-degree
relatives. Thus, the above findings should be treated cautiously.

Substance and alcohol use

The 9% dependency rate in the clinic group (all participants currently
depressed and 3 with psychotic illness) was lower than the 29% reported by
Fombonne et al
(2001). This may be owing to
our comparatively young follow-up age (mean 23 years), compared with a mean of
35 years in the Fombonne study. The high thresholds we set for diagnosis might
have resulted in an underestimate.

Deaths during follow-up

Although 46% of those from the clinic group had either self-harmed or
attempted suicide at the time of the index episode, there was no recorded
suicide during the follow-up period. This is somewhat surprising as the
strongest predictor of suicide is previous self-harm
(Safinofsky, 2000;
Hawton et al, 2003).
Other studies have reported moderate suicide rates. For example, Weissman
et al
(1999a) reported a
7.7% suicide rate; Harrington et al
(1990) reported 4 deaths (3%),
3 of which were suicide; and Fombonne et al
(2001) reported 8 deaths (3%),
6 of which were suicide. Our absence of suicides may be explained by our
cohort being relatively young at follow-up: mean age 23 years, compared with
means of 26 years, 31 years and 35 years respectively in the other
studies.

Clinical Implications and Limitations

CLINICAL IMPLICATIONS

Depression in the community requires early detection and psychiatric
assessment.

A significant proportion of young people with depression continue to be
depressed into young adult life.

Among clinically referred youngsters, course and outcome may differ between
the genders, with males showing increased risk of persistence and females of
recurrence.

LIMITATIONS

The small sample size limits the power of statistical analysis.

A significant proportion of the original group with pre-pubertal onset and
younger clinic patients were lost to follow-up.

The lengthy follow-up time may have resulted in selective recall or recall
bias.

Acknowledgments

We thank Carole Lack, Gillian Barker and Cessie Johannsson for data
collection; the staff at the Office for National Statistics; Sarah Vowler at
the Centre for Applied Medical Statistics, University of Cambridge; and Alison
Tamplin for advice. The study was funded by a grant from the Wellcome
Trust.